Pharmacological strategies that boost intracellular NAD + are highly coveted for their therapeutic potential. One approach is activation of nicotinamide phosphoribosyltransferase (NAMPT) to increase production of nicotinamide mononucleotide (NMN), the predominant NAD + precursor in mammalian cells. A high-throughput screen for NAMPT activators and hit-to-lead campaign yielded SBI-797812, a compound that is structurally similar to active-site directed NAMPT inhibitors and blocks binding of these inhibitors to NAMPT. SBI-797812 shifts the NAMPT reaction equilibrium towards NMN formation, increases NAMPT affinity for ATP, stabilizes phosphorylated NAMPT at His247, promotes consumption of the pyrophosphate by-product, and blunts feedback inhibition by NAD + . These effects of SBI-797812 turn NAMPT into a “super catalyst” that more efficiently generates NMN. Treatment of cultured cells with SBI-797812 increases intracellular NMN and NAD + . Dosing of mice with SBI-797812 elevates liver NAD + . Small molecule NAMPT activators such as SBI-797812 are a pioneering approach to raise intracellular NAD + and realize its associated salutary effects.

Objectives Dyslipidemia is a major risk issue for the development of cardiovascular disease. The aim of our study was to observe the pattern and prevalence of dyslipidemia in Pakistani population. Methodology This is a sub analysis of a population based second National Diabetes Survey of Pakistan (NDSP) 2016-2017 in adults aged 20 years or above, carried out from February 2016 to August 2017 across Pakistan. Multi stage sampling technique was used for the stratification of population, based on rural and urban domains. District wise clusters and sub clusters were selected i.e. 27 and 46 in number. Subjects, consented to participate were requested to come after an overnight fast for anthropometric measurements, oral glucose tolerance test and fasting lipid profile (except for subjects with self-reported diabetes). Dyslipidemia was identified using Adult Treatment Panel III guidelines. Results A total of 10,834 subjects (43.8% male and 56.2% female) having mean age of 43.8 ± 14.0 years, participated in the survey. Of the subjects studied, 39.3% had hypercholesterolemia, 48.9% had hypertriglyceridemia, 39.7% had high LDL-C levels while 83.9% men and 90% women had low HDL levels. High cholesterol and triglyceride levels were highest in 50-59 years age group, while high LDL and low HDL was most common in 40-49 years age group. Diabetes, obesity and hypertension were found to be the significant determinants for dyslipidemia. Conclusion Prevalence of dyslipidemia seems to be very high in Pakistan, necessitating an urgent call for early screening and effective management through lifestyle intervention and appropriate lipid lowering drugs to prevent this important cardiovascular risk factor.